Access to the opioid antidote naloxone is a critical component of addressing the opioid epidemic. Naloxone is a population-level prevention intervention associated with substantial reductions in overdose mortality. Furthermore, emerging data suggest that co-prescription of naloxone to people at risk of overdose from chronic opioid therapies may reduce negative health outcomes earlier in the risk horizon by avoiding nonfatal overdose. Expanding access to naloxone in the community through the pharmacy can be a critical mechanism for extending this lifesaving medication?s reach. Pharmacies exist in nearly every community and are staffed by knowledgeable health professionals trained in counseling patients about medication safety; many states also permit pharmacies to sell syringes over the counter for drug injection. Pharmacies? pivotal role in dispensing medications and selling syringes places them at the crossroads of opioid access and risk mitigation methods like naloxone provision. Testing ways to optimize pharmacy based naloxone (PBN) provision will be key as the country expands the implementation of naloxone through the medical system. We propose a large, practical study of a pharmacy- focused intervention to increase PBN dispensing and improve opioid safety. The intervention is comprised of two successful demonstration research projects (RESPOND, PI: Hartung; MOON Study, PI: Green, both R18), which include online and one-on-one educational outreach (i.e. academic detailing) demonstrated to provide knowledge and training for pharmacists to identify and effectively engage with patients who may be at high-risk for an opioid overdose. The overarching goal of this study is to reduce the number of opioid overdose deaths in the United States through greater access and use of naloxone, and safer opioid use. Uniquely, the study will draw from partnerships with two large retail pharmacy chains, CVS Pharmacy and Fred Meyer (a division of Kroger Corporation), who will provide a ?real-world? sample to support replicability and external validity. Specific aims are to: Aim 1: Integrate the MOON and RESPOND toolkit materials into one cohesive educational program (MOON+), and streamline the materials to enhance the focus on naloxone policy, communication, and administration; Aim 2: Using a stepped wedge, clustered randomized trial design, evaluate the effectiveness of MOON+ in 160 community pharmacies in increasing: a) PBN distribution rates, naloxone-related patient engagement, and pharmacists? attitudes, knowledge, perceived behavioral control and self-efficacy toward naloxone; and b) pharmacy syringe sales, and pharmacists? attitudes, knowledge, perceived behavioral control and self-efficacy toward dispensing buprenorphine for opioid use disorder (secondary outcomes). Aim 3: Applying a mixed methods approach, identify facilitators and barriers (e.g. state and store policies, regional characteristics) to implementation and effectiveness. Study findings will create a generalizable, evidence-based training and toolkit for pharmacists caring for patients who use prescribed or illicit opioids, in the over 40 states adopting or expanding pharmacy naloxone.